DESCRIPTION: (Applicant's Abstract) Drug research involving both humans and animals has focused predominately on the study of males. However, it is now apparent that men and women differ on several characteristics of drug addiction. These differences may be due to a real gender difference, or to sociocultural factors. Animal models that mimic the different phases of the addiction process might be useful in addressing this question. This project will focus on differences between male and female rats in three phases of the addiction process: acquisition, maintenance, and relapse. Additionally, it will investigate the contribution of the estrous cycle and ovarian hormones to any differences that are obtained. Acquisition of IV cocaine, heroin, and nicotine self-administration will be investigated using an autoshaping procedure. The criteria for acquisition of drug self-administration will be standardized across subjects and adjusted for dose and drug available. Regulation of cocaine, heroin, and nicotine intake will be-investigated using a two-lever drug self-administration procedure that allows the subject to increase and decrease their dose in discrete steps throughout an experimental session. The correlation between interdose interval and preceding dose size will be determined daily for each subject as a measure of regulation. Relapse to cocaine self-administration will be investigated using a priming model of drug reinstatement in which lever pressing for drug is extinguished by replacing drug infusions with saline infusions. Reinstatement of responding is then tested by administering a priming injection of drug. Specific aims are to compare in male and female rats: (1) the rate of acquisition of cocaine, heroin, and nicotine self-administration, (2) the effects of ovarian hormones on acquisition of cocaine, heroin, and nicotine self-administration, (3) regulation of cocaine, heroin, and nicotine intake, (4) regulation of cocaine, heroin, and nicotine intake across stages in the estrous cycle (in female rats) and, (5) relapse to cocaine self-administration as a function of priming dose of cocaine.